Channelopathies are a group of diseases caused by the dysfunction of

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

subunits or their interacting

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...

. These diseases can be inherited or acquired by other disorders, drugs, or toxins. Mutations in

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s encoding

s, which impair channel function, are the most common cause of channelopathies. There are more than 400 genes that encode ion channels, found in all human cell types and are involved in almost all physiological processes. Each type of channel is a multimeric complex of subunits encoded by a number of genes. Depending where the

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

occurs it may affect the gating, conductance, ion selectivity, or signal transduction of the channel. Channelopathies can be categorized based on the organ system which they are associated with. In the cardiovascular system, the electrical impulse needed for each heartbeat is made possible by the

electrochemical gradient An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts: * The chemical gradient, or difference in Concentration, solute concentration across ...

of each heart cell. Because the heartbeat is dependent on the proper movement of ions across the surface membrane, cardiac channelopathies make up a key group of heart diseases.

Long QT syndrome Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainti ...

, the most common form of cardiac channelopathy, is characterized by prolonged ventricular repolarization, predisposing to a high risk of ventricular tachyarrhythmias (e.g., torsade de pointes), syncope, and sudden cardiac death. The channelopathies of human

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

include hyper- and hypokalemic (high and low potassium blood concentrations)

periodic paralysis Periodic paralysis is a group of rare genetic diseases that lead to weakness or paralysis from common triggers such as cold, heat, high carbohydrate meals, not eating, stress or excitement and physical activity of any kind. The underlying mechani ...

myotonia congenita ''Myotonia congenita'' is a congenital neuromuscular channelopathy that affects skeletal muscles (muscles used for movement). It is a genetic disorder. The hallmark of the disease is the failure of initiated contraction to terminate, often refe ...

and

paramyotonia congenita ''Paramyotonia congenita'' (PC) is a rare congenital autosomal dominant neuromuscular disorder characterized by "paradoxical" myotonia. This type of myotonia has been termed paradoxical because it becomes worse with exercise whereas classical my ...

. Channelopathies affecting synaptic function are a type of synaptopathy.

Causes

Genetic type

Mutations in genes encoding ion channels, which cause defects in channel function, are the most common cause of channelopathies.

Acquired type

Acquired channelopathies are caused by acquired disorders, drug use, toxins, etc.

Types

The types in the following table are commonly accepted. Channelopathies currently under research, like Kir4.1 potassium channel in

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

, are not included.

Ion channels versus ion pumps

Both

channels Channel, channels, channeling, etc., may refer to: Geography * Channel (geography), a landform consisting of the outline (banks) of the path of a narrow body of water. Australia * Channel Country, region of outback Australia in Queensland and pa ...

and

pumps A pump is a device that moves fluids (liquids or gases), or sometimes slurries, by mechanical action, typically converted from electrical energy into hydraulic or pneumatic energy. Mechanical pumps serve in a wide range of applications such ...

are ion transporters which move ions across membranes. Channels move ions quickly, through

passive transport Passive transport is a type of membrane transport that does not require energy to move substances across cell membranes. Instead of using cellular energy, like active transport, passive transport relies on the second law of thermodynamics to ...

, down electrical and concentration gradients (moving "downhilll"); whereas pumps move ions slowly, through

active transport In cellular biology, active transport is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellula ...

, building-up gradients (moving "uphill"). Historically the difference between the two seemed cut and dried; however, recent research has shown that in some ion transporters, it is not always clear whether it functions as a channel or a pump. Diseases involving ion pumps can produce symptoms similar to channelopathies, as they both involve the movement of ions across membranes. Brody disease (also known as Brody myopathy) includes symptoms similar to

, including muscle stiffness and cramping after initiating exercise (delayed muscle relaxation). However, it is pseudo-

myotonia Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by delayed relaxation (prolonged contraction) of the skeletal muscles after voluntary contraction or electrical stimulation, and the muscle shows an abnor ...

as those with Brody disease have normal EMG. Due to similar symptoms, different genes for both channels and pumps can be associated with the same disease. For instance,

polymicrogyria Polymicrogyria (PMG) is a condition that affects the development of the human brain by multiple small gyri ( microgyri) creating excessive folding of the brain leading to an abnormally thick cortex. This abnormality can affect either one region of ...

has been associated with the channel gene

SCN3A Sodium channel, voltage-gated, type III, alpha subunit (SCN3A) is a protein that in humans is encoded by the ''SCN3A'' gene. Function Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit wi ...

and the pump gene

ATP1A3 Sodium/potassium-transporting ATPase subunit alpha-3 is an enzyme that in humans is encoded by the ''ATP1A3'' gene. Function The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of ...

, among other genes that are not ion transporters.

References

Bibliography

External links

VIDE
Channel Surfing in Pediatrics
by Carl E. Stafstrom, M.D., at the UW-Madison Health Sciences Learning Center. * *
Cystic Fibrosis Foundation

{{Membrane transport *